The long term goal of this project is to improve the metabolic complications of hyperinsulinemia in patients with polycystic ovary syndrome, hypertriglyceridemia, metabolic syndrome and type 2 diabetes mellitus by better understanding the newly-recognized dietary component pinitol. Pinitol (3-O-methyl-D-chiro-inositol) is a sugar related to myo-inositol, which is found in mammalian mediator molecules. Pinitol and its demethylated product D-chiro-inositol have been identified in small molecular weight bioactive inositol glycans from several different signaling pathways, including some related to insulin action. Treatment of patients with D-chiro-inositol or pinitol has been found to reduce insulin levels, lower hemoglobin Alc, lower elevated serum testosterone and reduce serum triglycerides in hyperinsulinemic patients. Our laboratory has established that pinitol, while very low in most foods, is a major component of legumes and citrus fruits, and that diet is a major contributor to body inositol levels. Pinitol is enzymatically converted to D-chiro-inositol in humans. We have developed a highly-sensitive inositol assay using gas chromatography/negative ion mass spectrometry that allows measurement of picomole amounts in serum and urine. The proposed work will test the hypothesis that, in human subjects, dietary pinitol administration elevates plasma pinitol and D-chiro-inositol levels and reduces plasma insulin, plasma free fatty acids and triglycerides. The kinetics of these inositols will be studied using specially-prepared deuterated tracers. This work will provide basic information about pinitol consumption, metabolism, kinetics and metabolic effects in hyperinsulinemic subjects. In the long term it may be possible to improve human hyperinsulinemic states by dietary recommendations or by recovering pinitol from food waste streams.